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Exposure to Metal Ions and Susceptibility to

Dental Caries
William H. Bowen, B.D.S., Ph.D.
Abstract: Results from several epidemiologic studies have shown that there are large differences in the prevalence of dental caries
from one region to another within the United States as well as in other countries. It has been postulated that the observed
differences may be attributed in part at least to exposure to trace elements such as selenium, vanadium, molybdenum, strontium,
and lead. Although data from epidemiologic studies usually support this hypothesis, direct evidence is sparse with the possible
exception of exposure to lead. Data from several epidemiologic studies and animal-based research support the concept that lead is
a caries-promoting element. Lead mimics calcium in several respects and may affect development of teeth and salivary glands,
clearly enhancing susceptibility to dental caries. Elevated blood levels are found most commonly in persons residing in inner
cities, particularly among the poor. Many states require blood lead level to be monitored in young children. Where feasible, these
records should form part of health history and be available to the treating dental practitioner to ensure that extra preventive
procedures may be implemented.
Dr. Bowen is Weicher Professor of Dentistry, Center for Oral Biology, University of Rochester. Direct correspondence to him at
the Center for Oral Biology, University of Rochester, 601 Elmwood Ave., Rochester, NY 14642; 716-275-0772 phone; 716-473-
2679 fax; William_Bowen@urmc.rochester.edu. The complete version of this paper can be viewed at http://www.nidcr.nih.gov/
news/consensus.asp.
Key words: lead, enamel, caries

T
he prevalence of dental caries varies signifi- to < 10 ug/dL.11 Some investigators regard even this
cantly from one region to another in the level to be more than 600 times higher than the natural
United States. Every national and regional sur- levels of lead in humans.12
vey of dental caries in children and adults supports these The adverse effects of lead on the oral tissues
observations.1-4 Less clear, however, are the reasons for have been noted for many centuries. Nikander, a Greek
these regional variations. It is unclear, for example, poet in the 2nd century B.C., as cited by Landrigan,8
whether the disparities observed can be attributed to noted the following regarding ingestion of cerusa (lead
enhanced resistance or increased susceptibility. Several carbonate):
hypotheses have been advanced to explain the phenom- The mouth it inflames and makes cold from
ena, ranging from exposure to trace metals, level of rain- within
fall, and hours of sunshine, to dietary practices. It is
The gums dry and wrinkled are parched like
well recognized that geological conditions (soil and
the skin
water) vary enormously from area to area although the
general opinion (with few exceptions) is that water is The rough tongue feels harsher the neck
not a major source of trace metals.5,6 muscles grip
The inadvertent ingestion of specific metals, in He soon cannot swallow foam runs from, his
particular lead, has been recognized as constituting a lip . . . .
major hazard to health for decades. Indeed, high blood Ramazzine (1713), also cited by Landrigan,8
lead levels are among the most prevalent childhood wrote about lead poisoning that “first their hands be-
conditions and the most prevalent environmental threats come palsied, then they become paralytic, splenetic,
to the health of children in the United States.7 lethargic and toothless.”
Few organ systems appear to escape its adverse In modern times, the number of children at risk
effects,8 although most attention has been focused on for developing lead poisoning is enormous, particularly
decreased intelligence and impaired neurobehavioral impoverished children who live in inner cities.13 About
development in children and adolescents.9 There are fourteen million or more children less than seven years
significant risks of toxicity even where individual of age are at enhanced risk because they reside in hous-
sources of lead are low, because all sources of lead are ing built before 1960.14,15 These houses harbor the high-
integrated systemically into critical target tissues.10 The est concentrations of lead paint. At least twenty million
margin of safety with lead is very narrow. The Centers houses have peeling lead-based paint; approximately
for Disease Control has lowered the acceptable con- four million of these are occupied by families with chil-
centration of lead in blood in young children from < 25 dren under seven years of age. Collectively, therefore,

1046 Journal of Dental Education ■ Volume 65, No. 10


it is estimated by the Centers for Disease Control16 that
890,000 (4.4 percent) of children in the United States How Exposure to Lead Could
aged one to five years have elevated levels of lead in
their blood (• 10 ug/dL) (BLL). The prevalence of el- Enhance Susceptibility to
evated BLLs was found to be 5.9 percent among chil-
dren aged one to two years; in older children (three to Caries
five years) the prevalence was 3.5 percent. Non-His-
There are several possible mechanisms through
panic black children (21.9 percent) and Mexican-Ameri-
which lead could enhance susceptibility to caries. In-
can children (13.0 percent) particularly those living in
formation on the effect of lead on enamel and dentine
older housing, appear to be particularly prone. It must
formation is sparse, even though considerable informa-
be emphasized that the risks of lead toxicity are not
tion has accumulated on lead concentrations in decidu-
limited to post-natal exposure. Lead readily crosses the
ous teeth in various communities. Furthermore, the re-
placenta and can affect the development and matura-
lationship between lead in blood and that in dentine
tion of several organ systems.17,18 Women of childbear-
has been explored.27
ing age represent between 40 percent and 50 percent of
Lead ions apparently act directly on bone min-
the total female population; it is estimated that approxi-
eral to replace calcium and phosphorus in the crystal
mately 4,460,000 residing in urban populations have
lattice and induce a hypercalcemia and a
blood levels (>10 ug/dL) that could impair healthy fe-
hyperphosphatemia.28 The incidence of enamel hypo-
tal development. Approximately 9 percent of these
plasia is increased in children and animals exposed to
women are pregnant at any one time; therefore, about
elevated levels of lead.28-30 A “lead line” was noted by
400,000 pregnancies are at risk for adverse health ef-
Appleton in the continuously erupting incisors of rats
fects from maternal lead in any given year.19,20 Clearly,
following a single injection of a large dose of lead ac-
for example, over a ten-year period, unless significant
etate.28 Further examination of this line revealed irregu-
efforts are made to abate pollution by lead, ten times
lar tubular structures and uneven mineralization, prob-
that number of fetuses will have been exposed to the
ably as a result of incomplete fusion of small
harmful effects of lead. Because of mobilization of lead
calcospherites. These observations suggest that lead may
from bone during pregnancy, transfer of lead to fetus is
affect odontoblast function and thereby influence den-
likely to be enhanced. In addition, it has been observed
tine formation. Support for this concept is found in the
that older women secrete more lead in their milk than
comprehensive review by Pounds, Lang, and Rosen who
do younger women: levels ranging from 0.24 to 35 ug/
show that lead intoxication directly and indirectly al-
dL have been reported.21
ters many aspects of bone cell function.24 Lead alters
Although there has been some lowering of blood
bone cell function through changes in 1,2,5
lead levels in some segments of the population during
dehydroxyvitamin D3; it may also perturb the ability
recent years, blood lead levels continue to be of con-
of cells to respond to hormonal regulation. Lead may
cern to African Americans, central city residents, resi-
impair the ability of cells to synthesize collagen or bone
dents in the northeast region of the United States, per-
sialoproteins and may directly affect or substitute for
sons with low income, and those with low educational
calcium in the active sites of the calcium and cAMP
attainment.16,22 It is interesting to note that these are the
messenger systems. Furthermore, Kato, Takimoto, and
persons and the regions where the highest prevalences
Ogura suggest that lead may have a direct effect on the
of caries are observed.
mineral phase of calcifying tissues.29 It has been postu-
Blood levels of lead give a clear indication of
lated that lead may first adsorb to hydroxyapatite crys-
current exposure to lead; however, they do not neces-
tals and later take positions within the structure.31,32
sarily accurately reflect the historic exposure to lead.
Featherstone, Nelson, and McLean observed wide dis-
Because lead mimics the effects of calcium in several
persal of lead by means of electron microscopy when
respects, it is readily incorporated in calcifying tis-
Pb hydroxyapatite is formed synthetically.33 Studies
sues.23,24 Enamel and dentine are usually not subject to
carried out in vitro34 using synthetic apatite crystals
significant remodeling, but the levels of lead in these
show that replacement of calcium by lead is a slow pro-
tissues (particularly circumpulpal dentine) are fre-
cess; however, in a dynamic mineralizing system, clearly
quently measured to assess children’s exposure to
lead can be incorporated into apatite rapidly, as shown
lead.25,26 Indeed, Needleman et al.’s study associating
by enhanced levels of lead in enamel and dentine of
lead with deficits in psychological and classroom per-
children ingesting elevated levels of lead. Results from
formance in children used lead levels in dentine as evi-
studies conducted by Grobler et al. showed that airborne
dence of exposure.9
lead is absorbed by rats and incorporated into develop-

October 2001 ■ Journal of Dental Education 1047


ing enamel and, further, that blood lead can become Thus based on available data, there is good, cred-
supplemented after direct exposure has ceased through ible evidence that ingestion of lead hypothetically could
mobilization from alveolar bone, as has been reported at least influence susceptibility to dental caries.
for other bones.35
Levels of lead as high as 4,000 ppm have been
found in the outer layers of enamel.36,37 Because of the
possibility of enamel acquiring lead post-eruptively, Present Study Objectives
particularly in contaminated environments, many in-
vestigators have used lead in dentine to determine ex-
and Search Methodology
posure to this element.27 Using this approach, Bercovitz Although there is much objective evidence for
and Laufer examined impacted teeth to determine the the role of many trace elements in the etiology of den-
absorption of lead into the body.38 They concluded that tal caries, the quality of the evidence rarely meets cur-
lead accumulates during formation of the dental tis- rent epidemiological or experimental standards.58 Fre-
sues; clearly, because lead readily crosses the placenta, quently, objective measurements of exposure to the
lead accumulates in the developing deciduous teeth.17 element of interest are lacking. I have chosen to focus
Presence of lead in the environment may also affect on lead because I consider it the only one for which
adversely the development and function of the salivary human exposure can be readily documented and ap-
glands. For example, rat salivary glands begin to de- propriate action by the dental practitioner may be imple-
velop at approximately embryonic day fifteen.39 Para- mented.
sympathetic innervation precedes sympathetic inner- Clearly, when exploring the published data, it
vation during the late prenatal period. 40 Both would have been unrealistic to expect to have found
sympathetic41-43 and parasympathetic44 denervation re- controlled clinical studies determining the effect of lead
tards gland development. Lead is known to produce on caries in humans. Much of the data supporting a
peripheral neuropathies such as slower maturation of role for lead in the etiology of caries comes from re-
synaptic density,45 reduction in conduction rates,46,47 and sults of epidemiologic studies that understandably vary
depression of pre-synaptic release of acetylcholine in in quality. In addition, significant data have been
the superior cervical ganglion.48,49 Many of the effects gleaned from animal studies that clarify the role of lead
of lead on the peripheral nervous system are apparently in the etiology of dental caries.
associated with its ability to inhibit Ca2+ uptake.49,50 I conducted detailed researches of the English-
Clearly perinatal exposure to lead could produce long- anguage literature from 1960 to January 2001 using
lasting influence on salivary function by interfering with MEDLINE. This proved to be more difficult than an-
normal autonomic nervous system-salivary gland in- ticipated because the word “lead” (which occurs fre-
teractions during development. quently in titles) can be confused with the metallic ele-
Lead also may act directly on gland tissue to in- ment “Lead.” In addition, I searched the so-called gray
hibit saliva formation. Heavy metals, in particular lead, literature which included old textbooks.5,59,60 I also
interfere with normal Ca2+ metabolism, acutely alter- searched theses from the University of Rochester, Roch-
ing normal cell function.51,23,52 Perturbation of Ca2+ me- ester, NY.
tabolism has severe consequences on salivary gland I included those studies conducted on humans
function; therefore, one of the most likely mechanisms only where the prevalence of caries was determined and
by which lead may acutely interfere with saliva forma- where a determination of exposure to lead could be
tion is its interaction with Ca2+ metabolism. Available confirmed. In three papers, we were unable to deter-
evidence, sparse as it is, clearly shows that administra- mine how a study was conducted or a simple statement
tion of lead results in significantly (30-40 percent) di- was made without data, so those were excluded.
minished stimulated salivary flow rates in rats.53,54 The I found 22,950 references to “dental caries,” 7,806
phenomenon has not been examined in humans. to “trace elements,” and 851 to “trace metals & caries.”
Lead appears to be concentrated in dental plaque, Search for “Lead” revealed 111,268 (see above). “Den-
that is, significantly more per unit is found there than tal plaque” yielded 10,658. Combination of “dental
in the surrounding saliva. For example, levels of 2•7 caries” and “lead” yielded 118; “dental caries “ and
ppm up to 54•7 ppm were reported in dental plaque by “trace elements,” 71. All of these were examined for
Schamschula and Bunzel55 and Beighton et al.56 It is their relevance to current review.
worthy of note that, in one study, elevated levels of lead In the animal-based studies (exclusively rats and
in plaque were associated with increased prevalence of hamsters), we included only those studies in which lead
caries.57 was included in diet and/or drinking water. Studies for

1048 Journal of Dental Education ■ Volume 65, No. 10


example of the topical application of lead fluoride were mental lead exposure itself or a factor that is directly
not included. linked to environmental lead exposure.”
The study conducted by Campbell, Moss, and
Raubertas also merits comment; it is one of a couple
that failed to show a relationship between ingestion of
Results lead and prevalence of caries.66 It is, however, impor-
The epidemiologic studies varied considerably in tant to emphasize the statement made by the authors
the methods used to determine exposure to lead. Of the that “the study lacked statistical power to demonstrate
twelve studies (Table 1) included, in four the relation- statistical significant correlations.”
ship of caries prevalence has been correlated with lead I detected just one animal study where lead
levels in soil/water. Clearly the approach is less than was administered throughout gestation. The resulting
completely satisfactory; analyses of enamel, plaque data show clearly that the susceptibility of rats exposed
blood, or other tissues would have offered supporting to lead pre- and perinatally is enhanced by close to 40
and confirmatory evidence that subjects did indeed in- percent. No evidence is available demonstrating that
gest lead. In five instances, lead was measured in teeth, exposure to lead post-eruptively has any effect on the
and even there different and distinct approaches were incidence of carious lesions.
used. In one, an enamel biopsy was used: in the course
of this study, it was shown that the level of lead de-
clines from surface to the enamel-dentin junction. An Comments
additional study used whole enamel as source, and as
expected, levels of lead were dramatically lower than Clearly epidemiologic studies on their own pro-
those found in teeth whose surface enamel was biopsied. vide less than completely satisfactory evidence. The
In three studies, whole teeth were used. In two studies, studies cited here provide an additional problem in that
levels of lead in blood were determined. Clearly, blood the source of lead to which correlations of caries preva-
levels were measured sometime after tooth develop- lence are made varies greatly. The best evidence of lead
ment; nevertheless, it is generally accepted that blood exposure is clearly analysis of lead in enamel. Blood
levels detected in the first years of life are indicative of lead levels in children also provide excellent evidence
longer term exposure. of exposure, but there is some uncertainty about whether
The methods used to measure the prevalence of it was elevated during tooth formation.
caries, also as expected, varied from study to study. In Somewhat surprisingly, few well-controlled ani-
some instances,61 there was probably underreporting mal studies have been carried out. The study of Wisotzky
because frank cavitation only was recorded. and Hein (Table 2) in hamsters showed that ingestion
Some of the studies warrant special comment. The of lead post-eruptively promoted development of car-
studies conducted by Anderson, Davies, and James,62 ies but only in male animals,67 which is a puzzling re-
Anderson and Davies,63 and Anderson et al.64 in the same sult. The study by Watson et al.54 provides clear and
area of Wales ten years apart yielded different results. unequivocal evidence of the influence of pre- and peri-
It is unclear whether the same level of pollution existed natal exposure on caries susceptibility in rats. Further-
over the ten-year period. In addition, it is particularly more, the model represents the situation that prevails
noteworthy that the prevalence of DMFT declined by in inner cities where young females grow in a lead-
over 50 percent in the same age groups over the ten- polluted environment. As a result, when these women
year span. are pregnant, their fetus is exposed to lead released from
Most of the studies included comparatively few its mother’s skeletal system and of course continuous
subjects with the obvious exception of the Moss et al. exposure to lead from the environment.
data.65 They used data from the NHANES III collected Clearly, no single study on its own provides un-
from 1988 to 1994, and suggest “the population attrib- equivocal proof that exposure to lead is caries- promot-
utable risk of lead exposure is estimated to be 13.5 per- ing; nevertheless, when the pattern of the epidemio-
cent of dental caries among individuals exposed to the logical studies is examined, combined with the data from
highest age-specific textile of lead level.” They further animals, one is inevitably drawn to the conclusion that
state that their “data further indicate that approximately lead does indeed enhance the susceptibility to dental
2.7 million excess cases of dental caries in older chil- caries.
dren and adolescents may be attributable to environ-

October 2001 ■ Journal of Dental Education 1049


1050
Table 1. Summary of epidemiologic studies

*Same areas re-examined after 10 years.


+
Appears to be same populations.

Journal of Dental Education ■ Volume 65, No. 10


Implications for Dental
Practitioners
Superficially, it may appear that once lead has
been incorporated into enamel, little can be accom-
plished towards alleviating its adverse effects. Clearly,
enamel biopsies are difficult and cumbersome for a
practitioner to conduct, and certainly are not part of
routine practice. However, the determination of levels
of lead in blood of very young children is now a routine
procedure and is required by law in several states; in-
deed, many states receive funds from the Centers for
Disease Control to develop surveillance systems. It
would be highly desirable to have such information as
part of patient clinical dental records. The practitioner
may then implement extra preventive procedures ap-
propriate for enhanced risk.
The most impoverished in society (Medicaid re-
cipients) show the highest prevalence of elevated blood
lead levels during childhood. Medicaid accounts for 60
percent of all children aged one to five years who have
elevated blood levels. Unfortunately, the recipients’
screening rates are deplorably low in Medicaid chil-
dren.16 Nevertheless, by eliciting a history of lead ex-
posure, the practitioner can enhance the public’s aware-
ness of the many adverse consequences of lead
exposure.

Need for Additional


Research
All the available data very clearly show large dis-
parities in the prevalence of dental caries from region
to region and even within regions. These differences
have persisted even when the incidence of dental caries
has declined following introduction of fluorides. There
have been few systematic studies to explore these im-
portant phenomena. The differences observed fre-
quently exceed those recorded following use of our most
Table 2. Summary of animal studies

successful therapeutic agents.


Lead is but one of many elements that apparently
has an influence on caries.5,68,69 The mechanism of ac-
tion of lead in increasing susceptibility to caries is not
completely solved, even though there appears to be a
sound rationale to explain its effects. The unraveling of
this mystery could provide insights into, for example,
“caries-susceptible teeth.”
Research into relationship trace metals, like se-
lenium, molybdenum, vanadium, and strontium, and
dental caries has in the past focussed largely on the ef-

October 2001 ■ Journal of Dental Education 1051


fect these may have on hard tissues. Their possible ef- 16. Centers for Disease Control. Blood lead levels in young
fects on plaque formation and metabolism have to a children—United States and selected states, 1996-1999.
large extent gone unexplored. Morb Mortal Wkly Rep 2000;49(50):1133-7.
17. Clark ARL. Placental transfer of lead and its effects on
Many trace elements work in concert with each
the newborn. Postgrad Med J 1977;53:674-8.
other, for example, copper and molybdenum. Fluoride 18. Goyer RA. Transplacental transport of lead. Environ
and aluminum may also interact. Many of the studies Health Perspect 1990;89:101-5.
of trace elements have involved investigating the ef- 19. Crocetti AF, Mushak P, Schwartz J. Determination of num-
fects of a single element, which may overlook impor- bers of lead-exposed U.S. children by areas of the United
tant interactions. Clearly, this whole area of research is States: an integrated summary of a report to the U.S. Con-
rich in promise and could be enormously rewarding. gress on childhood lead poisoning. Environ Health
Perspect 1990;89:109-20.
20. Crocetti AF, Mushak P, Schwartz J. Determination of num-
bers of lead-exposed women of childbearing age and preg-
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